The secretion of parathyroid hormone (PTH) by the parathyroid gland is directly regulated by extracellular calcium ions (Ca2+) via the Ca2+-sensing receptor. However, there are reports of magnesium (Mg2+) effect on PTH secretion: acute hypermagnesemia can suppress PTH and it is suggested that the mechanism of suppression is similar to that of hypercalcemia. During platelet apheresis, the infused citrate forms complexes with both Ca2+ and Mg2+ ions and, therefore, decreases the concentration of the bioactive forms ("ionized" Ca and Mg) of both cations in the blood returned to the donor. The resulting hypocalcemia and concomitant hypomagnesemia could influence the PTH response and could be responsible for the citrate toxicity symptoms observed during apheresis. We investigated the time course of changes in the concentrations of ionized Mg (iMg) and ionized Ca (iCa), and other electrolytes, which occur during plateletpheresis procedures in seven healthy donors undergoing three 90-min procedures each at fixed citrate infusion rates. Marked, progressive increases in serum citrate concentration occured during the rapid infusion of citrate that were accompanied by symptomatic decreases in iCa and iMg, and significantly increased renal excretion of calcium, magnesium and citrate.